The present invention relates to novel compounds having a neuron differentiation promoting activity and pharmaceutical use thereof.
Neurotrophic factors are proteinaceous compounds that participate in differentiation induction of neurons and in maintainance of the existence and survival of nerve cells. Nerve growth factors (hereinafter often abbreviated as NGF) are known to be representative of such compounds (Ann. Neuro., 10, 499-503 (1981)). It is manifested that NGF is deeply involved in the differentiation, existence maintenance and repair of neurons in both the central and peripheral nervous systems.
Damages of nerves caused by aging, internal and external factors often develop pathological symptoms. Such damages are found to cause, in the central nervous system, Alzheimer""s disease, dementia induced by cerebro-vascular disorders, disturbance of consciousness due to cerebral contusion, tremor or muscle rigidity by Parkinson""s disease, etc. It is also known that damages in the peripheral nervous system are induced by amyotrophic lateral sclerosis, spinal muscle atrophy, motor function disturbances due to neuron damages accompanied by accidents, etc., and that neuropathies are induced by diabetes mellitus, uremia, vitamin B1 or B12 deficiency , chronic liver disease, sarcoidosis, amyloidosis, hypothyrea, cancer, angiopathy, Sjxc3x6gren symptoms, immunopathy accompanied by infections, hereditary disease, physical compression, drugs (carcinostatic agents, tuberculostatic agents, anti-epileptic agents, etc.) or intoxication (arsenic, thallium, carbon disulfide, etc.); in more detail, see RINSHO KENSA (Clinical Test), 40, 760-766 (1996). It was the recognition in the art that when neurons suffer irreversible damages from these disorders, it was difficult to regenerate and repair the damaged neurons. However, on the hypothesis that neuropathy could be treated if the neurotrophic factors act on neurons, development of neurotrophic factors as medicaments against neuropathy has been made. (Science, 264, 772-774 (1994)). For instance, clinical trial of NGF is in progress against Alzheimer""s disease, neural damages or spinal injuries.
NGF is a series of proteins having approximately 50,000 molecular weight. For the treatment of neuropathy, it generally takes a long period of time. For these reasons, it is difficult to develop efficient administration and pharmaceutical formulation. Gene therapy namely induction of NGF gene, is also another choice for the treatment but its therapeutic effect is yet unclear.
It is known that when NGF is present, PC 12 cellsxe2x80x94which are the established cell line cloned from rat adrenal medulla pheochromocytomaxe2x80x94terminate cell proliferation and differentiate into neuron-like cells with neurites. This procedure enables to screen an effective substance having a NGF-like neuron differentiation promoting activity. For example, antibiotic staurosporin was found to have the PC 12 cell differentiation promoting activity (SHINKEI KAGAKU, 26, 200-220 (1987)). A similar differentiation promoting activity was recently observed in a biological active compound NK175203 (hereinafter referred to as cystacyclin) which was produced from Streptomyces sp. NK175203 strain FERM BP-4372 (WO 95/31992).
However, the toxicity and pharmacokinetics of staurosporin m vivo make its application as a medicament difficult. It has thus been strongly desired to develop a low molecular weight compound that exhibits a neuron differentiation promoting activity, is low toxic and is readily prepared synthetically.
The present inventors have made extensive investigations on cystacycline derivatives and as a result, have found novel compounds represented by general formulas [1A], [1B], [1C], [1D], [1E] and [1F] and pharmacologically acceptable salts thereof. The present invention has thus been accomplished. The present invention relates to the following compounds and compositions comprising the same.
1) A cyclopentanone derivative represented by a formula [1A]: 
wherein
XA is O, S, SO, SO2 or NH;
YA is a straight or branched aliphatic hydrocarbon group having 1 to 20 carbon atoms, which may be substituted or unsubstituted, or a substituted or unsubstituted aromatic hydrocarbon group or monocyclic aromatic heterocyclic ring having 3 to 6 carbon atoms;
each of Z1A, Z2A and Z3A, which may be the same or different and independently represents carboxy or a group derived therefrom, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms, hydroxy or a group derived therefrom, amino or a group derived therefrom, sulfonate or a group derived therefrom, phosphate or a group derived therefrom, a monocyclic heteroaryl, a halogen or hydrogen; or Z2A and Z3A are combined together to form a substituted or unsubstituted aromatic hydrocarbon or aromatic heterocyclic ring; and,
Z1A is carboxy or a group derived therefrom, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms, hydroxy or a group derived therefrom, amino or a group derived therefrom, a halogen or hydrogen, with the proviso that, when Z2A and Z3A are both hydrogen, Z1A is hydroxy or a group derived therefrom, amino or a group derived therefrom, sulfonate or a monocyclic aromatic heterocyclic ring, a halogen or hydrogen, and YA is a substituted or unsubstituted straight or branched aliphatic hydrocarbon group having 1 to 6 carbon atoms;
with the proviso that (1) through (7) are excluded:
(1) when Z1A and Z2A are hydrogen, XA is S, YA is methyl or benzyl and, Z3A is methoxycarbonyl,
(2) when Z1A and Z2A are hydrogen, XA is O or N, YA is benzyl and, Z3A is carboxy, methoxycarbonyl or ethoxycarbonyl;
(3) XA is N or O, Z1A and Z3A are hydrogen and, Z2A is carboxy or methoxycarbonyl;
(4) XA is O, Z1A is hydroxy or a group derived therefrom, Z2A is hydrogen and, Z3A is amino or a group derived therefrom;
(5) XA is S, Y1A is phenyl, Z1A is dimethoxymethyl and, Z2A and Z3A are hydrogen;
(6) XA is O, Y1A is methyl, Z1A is is 1-methoxy-1-phenylthiomethyl and, Z2A and Z3A are hydrogen;
(7) Z1A is S, SO or SO2, Z2A is hydroxy or a group derived therefrom and, Z3A is hydrogen;
or a pharmacologically acceptable salt thereof;
a 2,3-di-substituted cyclopentanone derivative of formula [1B]: 
xe2x80x83wherein:
XB is O, S, SO, SO2 or NH;
YB is:
an unsubstituted or substituted straight or branched aliphatic hydrocarbon group having 7 to 20 carbon atoms,
a straight or branched aliphatic hydrocarbon group having 1 to 6 carbon atoms, wherein:
at least one hydrogen is substituted with COW1 (wherein W1 is an unsubstituted or substituted aromatic heterocyclic ring or saturated heterocyclic ring) and, at least one hydrogen may be further substituted with a group derived from amino; or,
at least one hydrogen is substituted with NHCOV1 (wherein V1 is an alkyl having 2 to 5 carbon atoms containing 4 to 11 halogen atoms) and at least one hydrogen may be further substituted with carboxy or a group derived therefrom; or,
at least one hydrogen is substituted with a substituted or unsubstituted monocyclic aromatic heterocyclic ring and, at least one hydrogen may be further substituted with amino or a group derived therefrom; or,
a substituted or unsubstituted aromatic hydrocarbon group or monocyclic aromatic heterocyclic ring having 3 to 6 carbon atoms;
ZB is carboxy or a group derived therefrom, sulfonate or a group derived therefrom, phosphate or a group derived therefrom, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms, hydroxy, OR1 (wherein R1 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or, an unsubstituted or substituted acyl having 1 to 5 carbon atoms), NHCOR2 (wherein R2 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), NHSO2R2xe2x80x2 (wherein R2xe2x80x2 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or phenyl), a monocyclic aromatic heterocyclic ring, a halogen or hydrogen;
or a pharmacologically acceptable salt thereof;
a cyclopentenone derivative of formula [1C]: 
xe2x80x83wherein:
ring A has one double bond conjugated with oxo;
Xc is O, S, SO, SO2 or NH;
Yc is a substituted or unsubstituted aliphatic hydrocarbon group having 1 to 6 carbon atoms or a substituted or unsubstituted aromatic hydrocarbon group or monocyclic aromatic heterocyclic ring having 3 to 6 carbon atoms;
each of Z1c, Z2c and Z3c, which may be the same or different and independently represents carboxy or a group derived therefrom, hydroxy or a group derived therefrom, amino or a group derived therefrom, a substituted or unsubstituted alkyl or alkenyl having 1 to 4 carbon atoms, a monocyclic aromatic heterocyclic ring, a halogen atom or hydrogen;
with the proviso that, when Xc is O or NH, Z1c and Z3c are not hydrogen and, Z2c is not hydrogen or, hydroxy or a group derived therefrom;
or a pharmacologically acceptable salt thereof;
a ketone derivative of formula [1D]: 
xe2x80x83wherein:
AD is an unsubstituted or substituted aliphatic hydrocarbon group having 1 to 4 carbon atoms, an unsubstituted or substituted aromatic hydrocarbon, heterocyclic ring or saturated heterocyclic ring;
BD is hydrogen or an unsubstituted or substituted aliphatic hydrocarbon group having 1 to 4 carbon atoms; or,
AD and BD are combined together to form an unsubstituted or substituted cycloalkan-1-one ring having 3 to 7 carbon atoms (except for 5 carbon atoms);
XD is O, S, SO, SO2 or NH;
YD is a substituted or unsubstituted aliphatic hydrocarbon group having 1 to 6 carbon atoms or a substituted or unsubstituted aromatic hydrocarbon group or monocyclic aromatic heterocyclic ring having 3 to 6 carbon atoms;
ZD is carboxy or a group derived therefrom, an unsubstituted or substituted alkyl or alkenyl having 1 to 4 carbon atoms, hydroxy or a group derived therefrom, amino or a group derived therefrom, sulfonate or a group derived therefrom or, phosphate or a group derived therefrom, a monocyclic aromatic heterocyclic ring, a halogen or hydrogen;
with the proviso that, when AD and BD are combined together to form a cyclobutane ring, the following (1) through (4) are excluded:
(1) XD is O, YD is methyl, n-octyl or n-hexadecyl and, ZD is methoxycarbonyl;
(2) XD is O, YD is benzyl and, ZD is benzyloxylmethyl;
(3) XD is O, YD is p-methoxybenzyl and, ZD is p-methoxybenzyloxymethyl; and,
(4) XD is O, YD is trityl and ZD is trityloxymethyl or, when AD is an unsubstituted benzene ring and BD is hydrogen, XD is S, YD is methyl, ethyl or isopropyl and ZD is carboxy;
or a pharmacologically acceptable salt thereof;
a compound of formula [1E]: 
or a pharmacologically acceptable salt thereof; or,
a xcex2-di-substituted aminoketone derivative of formula [1F]: 
xe2x80x83wherein:
AF is an unsubstituted or substituted aliphatic hydrocarbon group having 1 to 4 carbon atoms or, an unsubstituted or substituted aromatic hydrocarbon ring, aromatic heterocyclic ring or saturated heterocyclic ring;
BF is hydrogen or, an unsubstituted or substituted aliphatic hydrocarbon group having 1 to 4 carbon atoms; or,
AF and BF are combined together to form an unsubstituted or substituted cycloalkan-1-one ring having 3 to 7 carbon atoms or, to form a cycloalkan-1-one ring having 3 to 7 carbon atoms and fused with an aromatic hydrocarbon or a aromatic heterocyclic ring;
each of XF and YF is an unsubstituted or substituted straight or branched aliphatic hydrocarbon group having 1 to 10 carbon atoms or, XF and YF are bound to each other directly or via a hetero atom to form an unsubstituted or substituted heterocyclic ring;
ZF is carboxy or a group derived therefrom, an unsubstituted or substituted alkyl or alkenyl having 1 to 4 carbon atoms, hydroxy or a group derived therefrom, amino or a group derived therefrom, sulfonate or a group derived therefrom, phosphate or a group derived therefrom, a monocyclic aromatic heterocyclic ring or a halogen;
with the proviso that, when AF is an unsubstituted benzene ring, excluded are those wherein BF is hydrogen, XF and YF are bound to each other directly to form a piperidine ring and, ZF is carboxy; or a pharmacologically acceptable salt thereof.
2) A cyclopentanone derivative of formula [1A] or a pharmacologically acceptable salt thereof, according to 1) above, wherein:
XA is S, O, S or SO;
YA is a straight or branched aliphatic hydrocarbon group having 1 to 20 carbon atoms (wherein at least one hydrogen atom is substituted with carboxy or a group derived therefrom, or amino or a group derived therefrom);
each of Z1A, Z2A and Z3A, which may be the same or different and independently represents carboxy or a group derived therefrom, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms, hydroxy or a group derived therefrom, amino or a group derived therefrom, a monocyclic aromatic heterocyclic ring, a halogen or hydrogen; or Z2A and Z3A are combined together to form a substituted or unsubstituted aromatic hydrocarbon or a aromatic heterocyclic ring; and,
Z1A is carboxy or a group derived therefrom, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms, hydroxy or a group derived therefrom, amino or a group derived therefrom, a halogen or hydrogen.
3) A cyclopentanone derivative of formula [1A] or a pharmacologically acceptable salt thereof, according to 2) described above, wherein:
XA is S;
YA is a straight or branched aliphatic hydrocarbon group having 1 to 6 carbon atoms, wherein;
at least one hydrogen atom is substituted with carboxy, COOR1 (wherein R1 is a substituted or unsubstituted alkyl, alkenyl or alkynyl having 1 to 4 carbon atoms), COW1 (wherein W1 is a heterocyclic ring unsubstituted or substituted with carboxy or a group derived therefrom) or NR2R3 (wherein each of R2 and R3, which may be different or the same independently, represents hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or, an unsubstituted or substituted acyl having 1 to 5 carbon atoms);
each of Z1A, Z2A and Z3A, which may be the same or different and independently represents carboxy, COOR4 (wherein R4 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), CONR5R6 (wherein each of R5 and R6, which may be different or the same independently, represents hydrogen or a substituted or unsubstituted alkyl having 1 to 4 carbon atoms), cyano, hydroxy, OR7 (wherein R7 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or, an unsubstituted or substituted acyl having 1 to 5 carbon atoms), NR8R9 (wherein each of R8 and R9, which may be the same or different and independently represents hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or, an unsubstituted or substituted acyl having 1 to 5 carbon atoms), CH2OR10 (wherein R10 is hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or, an unsubstituted or substituted acyl having 1 to 5 carbon atoms), chlorine, fluorine or hydrogen; or,
Z2A and Z3A are combined together to form a substituted or unsubstituted aromatic hydrocarbon; and,
Z1A is carboxy, COOR4 (wherein R4 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), CONR5R6 (wherein each of R5 and R6, which may be different or the same independently, represents hydrogen or a substituted or unsubstituted alkyl having 1 to 4 carbon atoms), cyano, hydroxy, OR7 (wherein R7 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or, an unsubstituted or substituted acyl having 1 to 5 carbon atoms), NR8R9 (wherein each of R8 and R9 which may be the same or different and independently represents hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or, an unsubstituted or substituted acyl having 1 to 5 carbon atoms), CH2OR10 (wherein R10 is hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or, an unsubstituted or substituted acyl having 1 to 5 carbon atoms), chlorine, fluorine or hydrogen.
4) A cyclopentanone derivative of formula [1A] or a pharmacologically acceptable salt thereof, according to 3) described above, wherein:
XA is S;
YA is a straight aliphatic hydrocarbon group having 1 to 6 carbon atoms, wherein:
at least two hydrogen atoms are substituted with any of carboxy, COOR1xe2x80x2 (wherein R11 is an alkyl, alkenyl or alkynyl having 1 to 4 carbon atoms), COW2 (wherein W2 is a saturated heterocyclic ring unsubstituted or substituted with COOR11 (wherein R11 is an alkyl having 1 to 4 carbon atoms) or NHCOR12 (wherein R12 is an alkyl having 1 to 4 carbon atoms);
each of Z1A, Z2A and Z3A, which may be the same or different and independently represents carboxy, COOR4xe2x80x2 (wherein R4xe2x80x2 is an alkyl having 1 to 4 carbon atoms), hydroxy, OCOR13 (wherein R13 is an alkyl having 1 to 4 carbon atoms), CH2OR10xe2x80x2 (wherein R10xe2x80x2 is hydrogen, an alkyl having 1 to 4 carbon atoms or an acyl having 1 to 5 carbon atoms), or hydrogen; or,
Z2A and Z3A are combined together to form a benzene ring unsubstituted or substituted with an alkyl having 1 to 4 carbon atoms, an alkyloxy having 1 to 4 carbon atoms, nitro, trifluoromethyl or halogen; and,
Z1A is carboxy, COOR4xe2x80x2 (wherein R4xe2x80x2 is an alkyl having 1 to 4 carbon atoms), hydroxy, OCOR13 (wherein R13 is an alkyl having 1 to 4 carbon atoms), CH2OR10xe2x80x2 (wherein R10xe2x80x2 is hydrogen, an alkyl having 1 to 4 carbon atoms or an acyl having 1 to 5 carbon atoms), or hydrogen.
5) A cyclopentanone derivative of formula [1A] or a pharmacologically acceptable salt thereof, according to 4) described above, wherein:
XA is S;
YA is a straight aliphatic hydrocarbon group having 1 to 6 carbon atoms, wherein:
one hydrogen is substituted with carboxy, methoxycarbonyl, COW3 (wherein W3 is a pyrrolidine, piperidine, azetidine, morpholine or piperazine ring, which may be unsubstituted or substituted with methoxycarbonyl) and one other hydrogen is substituted with acetylamino;
each of Z1A, Z2A and Z3A, which may be the same or different and independently represents carboxy, methoxycarbonyl, hydroxy, acetyloxymethyl, hydroxymethyl or hydrogen; or,
Z2A and Z3A are combined together to form unsubstituted benzene ring; and,
Z1A is carboxy, methoxycarbonyl, hydroxy, acetyloxymethyl, hydroxymethyl or hydrogen.
6) A cyclopentanone derivative of formula [1A] or a pharmacologically acceptable salt thereof, according to 5) described above, wherein the cyclopentanone derivative is selected from the group consisting of:
(I) XA is S, YA is 2-acetylamino-2-carboxyethyl, Z1A and Z3A are hydrogen and, Z2A is carboxy;
(II) XA is S, YA is 2-acetylamino-2-methoxycarbonylethyl, Z1A and Z3A are hydrogen and, Z2A is carboxy;
(III) XA is S, YA is 2-acetylamino-2-carboxyethyl, Z1A and Z3A are hydrogen and, Z2A is hydroxy;
(IV) XA is S, YA is 2-acetylamino-3-oxo-3-{1-(2-methoxycarbonyl)pyrrolidinyl}propyl, Z1A and Z3A are hydrogen and, Z2A is hydroxy;
(V) XA is S, YA is 2-acetylamino-2-methoxycarbonylethyl, Z2A and Z3A are combined together to form an unsubstituted benzene ring and, Z1A is carboxy; and,
(VI) XA is S, YA is 2-acetylamino-2-carboxyethyl, Z2A and Z3A are combined together to form an unsubstituted benzene ring and, Z1A is carboxy.
7) A 2,3-di-substituted cyclopentanone derivative of formula [1B] or a pharmacologically acceptable salt thereof, according to 1) above, wherein:
XB is S, O or SO;
YB is a straight or branched aliphatic hydrocarbon group having 7 to 20 carbon atoms (wherein at least one hydrogen may optionally be substituted with carboxy or a group derived therefrom or, amino or a group derived therefrom); and,
ZB is carboxy, COOR3 (wherein R3 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), CH2OR4 (wherein R4 is hydrogen or an unsubstituted or substituted alkyl having 1 to 4 carbon atoms) or, CH2OCOR5 (wherein R5 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms).
8) A 2,3-di-substituted cyclopentanone derivative of formula [1B] or a pharmacologically acceptable salt thereof, according to 7) described above, wherein:
XB is S;
YB is a straight aliphatic hydrocarbon group having 7 to 20 carbon atoms (wherein at least two hydrogen atoms are substituted with carboxy, COOR6 (wherein R6 is an alkyl, alkenyl or alkynyl having 1 to 4 carbon atoms) or NR7R8 (wherein each of R7 and R8, which may be the same or different and independently represents hydrogen, an alkyl having 1 to 4 carbon atoms or an acyl having 1 to 5 carbon atoms); and,
ZB is carboxy, methoxycarbonyl, hydroxymethyl or acetyloxymethyl.
9) A 2,3-di-substituted cyclopentanone derivative of formula [1B] or a pharmacologically acceptable salt thereof, according to 8) described above, wherein:
XB is S;
YB is 11-acetylamino-11-carboxy-n-undecyl; and,
ZB is carboxy.
10) A 2,3-di-substituted cyclopentanone derivative of formula [1B] or a pharmacologically acceptable salt thereof, according to 1) above, wherein:
XB is S, O or SO;
YB is a straight or branched aliphatic hydrocarbon group having 1 to 6 carbon atoms wherein at least one hydrogen is substituted with COW2 {wherein W2 is a saturated heterocyclic ring unsubstituted or substituted with carboxy, a hydroxyalkyl having 1 to 4 carbon atoms, phenyl or COOR9 (wherein R9 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms)} and, at least one other hydrogen is substituted with NR10R11 (wherein each of R10 and R11, which may be the same or different and independently represents hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or, an unsubstituted or substituted acyl having 1 to 5 carbon atoms); and,
ZB is carboxy, COOR3 (wherein R3 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), CH2OR4 (wherein R4 is hydrogen or an unsubstituted or substituted alkyl having 1 to 4 carbon atoms) or, CH2OCOR5 (wherein R5 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms).
11) A 2,3-di-substituted cyclopentanone derivative of formula [1B] or a pharmacologically acceptable salt thereof, according to 10) described above, wherein:
XB is S;
YB is a straight or branched aliphatic hydrocarbon group having 1 to 6 carbon atoms {wherein one hydrogen is substituted with COW3 (wherein W3 is a 1-azetidinyl, 1-piperidyl, 1-pyrrolidinyl, 1-piperazinyl or 4-morpholinyl group, which group may be unsubstituted or substituted with carboxy, methoxycarbonyl, 2-hydroxyethyl, phenyl or tert-butoxycarbonyl) and one other hydrogen is substituted with NHCOR12 (wherein R12 is an alkyl having 1 to 4 carbon atoms)}; and,
ZB is carboxy, methoxycarbonyl, hydroxymethyl or acetyloxy.
12) A 2,3-di-substituted cyclopentanone derivative of formula [1B] described in 1) above or a pharmacologically acceptable salt thereof, according to 11) described above, wherein:
XB is S;
YB is 2-acetylamino-3-oxo-3-(1-pyrrolidinyl)propyl, 2-acetylamino-3-{1-(2-methoxycarbonyl)pyrrolidinyl-3-oxopropyl, 2-acetylamino-3-oxo-3-(1-piperidyl)propyl, 2-acetylamino-3-(4-morpholinyl)-3-oxopropyl, 2-acetylamino-3-{1-(2-methoxycarbonyl)azetidinyl}-3-oxopropyl, 2-acetylamino-3-oxo-3-(1-piperazinyl)propyl, 2-acetylamino-3-[1-{4-(2-hydroxyethyl)piperazinyl}]-3-oxopropyl, 2-acetylamino-3-{1-(4-phenylpiperazinyl)}-3-oxopropyl or 2-acetylamino-3-{1-(4-tert-butoxycarbonylpiperazinyl)}-3-oxopropyl; and,
ZB is carboxy or methoxycarbonyl.
13) A 2,3-di-substituted cyclopentanone derivative of formula [1B] described in 1) above or a pharmacologically acceptable salt thereof, according to 1) above, wherein:
XB is S, O or SO;
YB is a straight or branched aliphatic hydrocarbon group having 1 to 6 carbon atoms {wherein at least one hydrogen is substituted with NHCOV1 (wherein V1 is an alkyl having 2 to 5 carbon atoms and containing 4 to 11 halogen atoms) and, at least one other hydrogen may be further substituted with carboxy or COOR13 (wherein R13 is an unsubstituted or substituted alkyl, alkenyl or alkynyl having 1 to 4 carbon atoms)}; and,
ZB is carboxy, COOR3 (wherein R3 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), CH2OR4 (wherein R4 is hydrogen or an unsubstituted or substituted alkyl having 1 to 4 carbon atoms) or CH2OCOR5 (wherein R5 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms).
14) A 2,3-di-substituted cyclopentanone derivative of formula [1B] described in 1) above or a pharmacologically acceptable salt thereof, according to 13) described above, wherein:
XB is S;
YB is a straight aliphatic hydrocarbon group having 1 to 6 carbon atoms {wherein one hydrogen is substituted with NHCOV2 (wherein V2 is an alkyl having 2 to 5 carbon atoms and containing 4 to 11 fluorine atoms) and, one other hydrogen is further substituted with carboxy or COOR13xe2x80x2 (wherein R13xe2x80x2 is an alkyl, alkenyl or alkynyl having 1 to 4 carbon atoms)}; and,
ZB is carboxy, methoxycarbonyl, hydroxymethyl or acetyloxymethyl.
15) A 2,3-di-substituted cyclopentanone derivative of formula [1B] described in 1) above or a pharmacologically acceptable salt thereof, according to 14) described above, wherein:
XB is S;
YB is 2-carboxy-2-(pentafluoropropionyl)aminoethyl; and,
ZB is carboxy or hydroxymethyl.
16) A 2,3-di-substituted cyclopentanone derivative of formula [1B] described in 1) above or a pharmacologically acceptable salt thereof, according to 1) above, wherein:
XB is S, O or SO;
YB is a straight or branched aliphatic hydrocarbon group having 1 to 6 carbon atoms {wherein at least one hydrogen is substituted with a substituted or unsubstituted monocyclic aromatic heterocyclic ring and at least one other hydrogen is further substituted with NR15R16 (wherein each of R15 and R16, which may be the same or different and independently represents hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms, or an unsubstituted or substituted acyl having 1 to 5 carbon atoms)}; and,
ZB is carboxy, COOR3 (wherein R3 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), CH2OR4 (wherein R4 is hydrogen or an unsubstituted or substituted alkyl having 1 to 4 carbon atoms) or CH2OCOR5 (wherein R5 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms).
17) A 2,3-di-substituted cyclopentanone derivative of formula [1B] described in 1) above or a pharmacologically acceptable salt thereof, according to 16) described above, wherein:
XB is S;
YB is a straight aliphatic hydrocarbon group having 1 to 4 carbon atoms {wherein one hydrogen should be substituted with a pyridine ring unsubstituted or substituted with an alkyl having 1 to 4 carbon atoms or with 5-tetrazolyl, and one other hydrogen may be further substituted with NHCOR17 (wherein R17 is an alkyl having 1 to 4 carbon atoms}; and,
ZB is carboxy, methoxycarbonyl, hydroxymethyl or acetyloxymethyl.
18) A 2,3-di-substituted cyclopentanone derivative of formula [1B] described in 1) above or a pharmacologically acceptable salt thereof, according to 17) described above, wherein:
XB is S;
YB is 3-(3-pyridyl)propyl, 3-{3-(1-methylpyridinium iodide)}propyl or 2-acetylamino-2-(5-tetrazolyl)ethyl;
ZB is carboxy or methoxycarbonyl.
19) A cyclopentenone derivative of formula [1C] described in 1) above or a pharmacologically acceptable salt thereof, according to 1) above, wherein:
ring A forms an oxo-conjugated double bond together with the carbon atom bound to CH2-Xc-Yc;
Xc is S, O or SO;
Yc is an aliphatic hydrocarbon group having 1 to 6 carbon atoms (wherein at least one hydrogen is substituted with carboxy or a group derived therefrom, amino or a group derived therefrom or, hydroxy or a group derived therefrom); and,
each of Z1c, Z2c and Z3c, which may be the same or different and independently represents carboxy or a group derived therefrom, hydroxy or a group derived therefrom, amino or a group derived therefrom, a substituted or unsubstituted alkyl or alkenyl having 1 to 4 carbon atoms, a monocyclic aromatic heterocyclic ring, a halogen or hydrogen.
20) A cyclopentenone derivative of formula [iC] described in 1) above or a pharmacologically acceptable salt thereof, according to 19) described above, wherein:
ring A forms an oxo-conjugated double bond together with the carbon atom bound to CH2xe2x80x94Xcxe2x80x94Yc;
Xc is S, O or SO;
Yc is an aliphatic hydrocarbon group having 1 to 6 carbon atoms (wherein at least one hydrogen is substituted with carboxy, COOR1 (wherein R1 is a substituted or unsubstituted alkyl or alkenyl having 1 to 4 carbon atoms), CONR2R3 (wherein each of R2 and R3 which may be the same or different and independently represents hydrogen or an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), COW (wherein W is a heterocyclic ring unsubstituted or substituted with carboxy or a group derived therefrom or, amino or a group derived therefrom), NR4R5 (wherein each of R4 and R5, which may be the same or different and independently represents hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or, an unsubstituted or substituted acyl having 1 to 5 carbon atoms) or OR6 (wherein R6 is hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or, an unsubstituted or substituted acyl having 1 to 5 carbon atoms); and,
each of Z1c, Z2c and Z3c independently represents carboxy, COOR7 (wherein R7 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), CONR8R9 (wherein each of R8 and R9, which may be the same or different and independently represents hydrogen or an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), cyano, CH2OR10 (wherein R10 is hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or, an unsubstituted or substituted acyl having 1 to 5 carbon atoms), hydroxy, OCOR11 (wherein R11 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), NR12R13 (wherein each of R12 and R13, which may be the same or different and independently represents hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or, an unsubstituted or substituted acyl having 1 to 5 carbon atoms), 5-tetrazolyl, chlorine, fluorine or hydrogen.
21) A cyclopentenone derivative of formula [1C] described in 1) above or a pharmacologically acceptable salt thereof, according to 20) described above, wherein:
ring A forms an oxo-conjugated double bond together with the carbon atom bound to CH2xe2x80x94Xcxe2x80x94Yc;
Xc is S;
Yc is an aliphatic hydrocarbon group having 1 to 6 carbon atoms (wherein at least two hydrogen atoms are substituted with carboxy, COOR1xe2x80x2 (wherein R1xe2x80x2 is an alkyl or alkenyl having 1 to 4 carbon atoms), NHCOR14 (wherein R14 is an alkyl having 1 to 4 carbon atoms which hydrogen may optionally be substituted with fluorine), hydroxy, or OCOR15 (wherein R15 is an alkyl having 1 to 4 carbon atoms); and,
each of Z1c, Z2c and Z3c is carboxy, COOR7xe2x80x2 (wherein R7xe2x80x2 is an alkyl having 1 to 4 carbon atoms) or CH2OR10xe2x80x2 (wherein R10xe2x80x2 is hydrogen or an acyl having 1 to 5 carbon atoms).
22) A cyclopentenone derivative of formula [1C] described in 1) above or a pharmacologically acceptable salt thereof, according to 21) described above, wherein:
ring A forms an oxo-conjugated double bond together with the carbon atom bound to CH2xe2x80x94Xcxe2x80x94Yc;
Xc is S;
Yc is 2-acetylamino-2-carboxyethyl; and,
either Z1c or Z2c is hydroxy and the remaining groups out of Z1c, Z2c and Z33 are all hydrogen.
23) A cyclopentenone derivative of formula [1C] described in 1) above or a pharmacologically acceptable salt thereof, according to 1) above, wherein:
ring A forms an oxo-conjugated double bond without containing the carbon atom bound to CH2xe2x80x94Xcxe2x80x94Yc;
Xc is S, O or SO;
Yc is an aliphatic hydrocarbon group having 1 to 6 carbon atoms (wherein at least one hydrogen is substituted with carboxy or a group derived therefrom, amino or a group derived therefrom or, hydroxy or a group derived therefrom); and,
each of Z1c, Z2c and Z3c is carboxy or a group derived therefrom, an unsubstituted or substituted alkyl or alkenyl having 1 to 4 carbon atoms, hydroxy or a group derived therefrom, amino or a group derived therefrom, a monocyclic aromatic heterocyclic ring, a halogen or hydrogen.
24) A cyclopentenone derivative of formula [1C] described in 1) above or a pharmacologically acceptable salt thereof, according to 23) described above, wherein:
ring A forms an oxo-conjugated double bond without containing the carbon atom bound to CH2xe2x80x94Xcxe2x80x94Yc;
Xc is S, O or SO;
Yc is an aliphatic hydrocarbon group having 1 to 6 carbon atoms (wherein at least one hydrogen is substituted with carboxy, COOR1 (wherein R1 is a substituted or unsubstituted alkyl or alkenyl having 1 to 4 carbon atoms), CONR2R3 (wherein each of R2 and R3 which may be the same or different and independently represents hydrogen or an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), COW (wherein W is a heterocyclic ring unsubstituted or substituted with carboxy or a group derived therefrom or, amino or a group derived therefrom), NR4R5 (wherein each of R4 and R5, which may be the same or different and independently represents hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or, an unsubstituted or substituted acyl having 1 to 5 carbon atoms) or OR6 (wherein R6 is hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or, an unsubstituted or substituted acyl having 1 to 5 carbon atoms); and,
each of Z1c, Z2c and Z3c independently represents carboxy, COOR7 (wherein R7 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), CONR8R9 (wherein each of R8 and R9, which may be the same or different and independently represents hydrogen or an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), cyano, CH2OR10 (wherein R10 is hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or, an unsubstituted or substituted acyl having 1 to 5 carbon atoms), hydroxy, OCOR11 (wherein R11 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), NR12R13 (wherein each of R12 and R13, which may be the same or different and independently represents hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or, an unsubstituted or substituted acyl having 1 to 5 carbon atoms), 5-tetrazolyl, chlorine, fluorine or hydrogen.
25) A cyclopentenone derivative of formula [1C] described in 1) above or a pharmacologically acceptable salt thereof, according to 24) described above, wherein:
ring A forms an oxo-conjugated double bond without containing the carbon atom bound to CH2xe2x80x94Xcxe2x80x94Yc;
Xc is S;
Yc is an aliphatic hydrocarbon group having 1 to 6 carbon atoms (wherein at least two hydrogen atoms are substituted with carboxy, COOR1xe2x80x2 (wherein R1xe2x80x2 is an alkyl or alkenyl having 1 to 4 carbon atoms), NHCOR14 (wherein R14 is an alkyl having 1 to 4 carbon atoms which hydrogen may optionally be substituted with fluorine), hydroxy or OCOR15 (wherein R15 is an alkyl having 1 to 4 carbon atoms); and,
each of Z1c, Z2c and Z33 is carboxy, COOR7xe2x80x2 (wherein R7xe2x80x2 is an alkyl having 1 to 4 carbon atoms) or CH2OR10xe2x80x2 (wherein R10xe2x80x2 is hydrogen or an acyl having 1 to 5 carbon atoms).
26) A cyclopentenone derivative of formula [1C] described in 1) above or a pharmacologically acceptable salt thereof, according to 25) described above, wherein:
ring A forms an oxo-conjugated double bond without containing the carbon atom bound to CH2xe2x80x94Xcxe2x80x94Yc;
Xc is S;
Yc is 2-acetylamino-2-carboxyethyl; and,
all of Z1c, Z2c and Z3c are hydrogen.
27) A ketone derivative of formula [1D] described in 1) above or a pharmacologically acceptable salt thereof, according to 1) above, wherein:
AD is an unsubstituted or substituted aliphatic hydrocarbon group having 1 to 4 carbon atoms;
BD is hydrogen or an unsubstituted or substituted aliphatic hydrocarbon group having 1 to 4 carbon atoms;
XD is S, O, or SO;
YD is an aliphatic hydrocarbon group having 1 to 6 carbon atoms (wherein at least one hydrogen is substituted with carboxy or a group derived therefrom, amino or a group derived therefrom or, hydroxy or a group derived therefrom); and,
ZD is carboxy or a group derived therefrom, an unsubstituted or substituted alkyl or alkenyl having 1 to 4 carbon atoms, hydroxy or a group derived therefrom, amino or a group derived therefrom, a monocyclic aromatic heterocyclic ring, a halogen or hydrogen.
28) A ketone derivative of formula [1D] described in 1) above or a pharmacologically acceptable salt thereof, according to 27) described above, wherein:
AD is an aliphatic hydrocarbon group having 1 to 4 carbon atoms;
BD is hydrogen or an aliphatic hydrocarbon group having 1 to 4 carbon atoms;
XD is S, O, or SO;
YD is an aliphatic hydrocarbon group having 1 to 6 carbon atoms (wherein at least one hydrogen is substituted with carboxy, COOR1 (wherein R1 is a substituted or unsubstituted alkyl or alkenyl having 1 to 4 carbon atoms), CONR2R3 (wherein each of R2 and R3 which may be the same or different and independently represents hydrogen or an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), COW (wherein W is a heterocyclic ring unsubstituted or substituted with carboxy or a group derived therefrom or, amino or a group derived therefrom), NR4R5 (wherein each of R4 and R5, which may be the same or different and independently represents hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or, an unsubstituted or substituted acyl having 1 to 5 carbon atoms) or OR6 (wherein R6 is hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or, an unsubstituted or substituted acyl having 1 to 5 carbon atoms); and,
ZD is carboxy, COOR7 (wherein R7 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), CONR8R9 (wherein each of R8 and R9, which may be the same or different and independently represents hydrogen or an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), cyano, CH2OR10 (wherein R10 is hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or, an unsubstituted or substituted acyl having 1 to 5 carbon atoms), hydroxy, OCOR11 (wherein R11 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), NR12R13 (wherein each of R12 and R13 which may be the same or different and independently represents hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or, an unsubstituted or substituted acyl having 1 to 5 carbon atoms), 5-tetrazolyl, chlorine, fluorine or hydrogen.
29) A ketone derivative of formula [1D] described in 1) above or a pharmacologically acceptable salt thereof, according to 28) described above, wherein:
AD is an alkyl having 1 to 4 carbon atoms;
BD is hydrogen or an alkyl having 1 to 4 carbon atoms;
XD is S;
YD is an aliphatic hydrocarbon group having 1 to 6 carbon atoms (wherein at least two hydrogen atoms are substituted with carboxy, COOR1xe2x80x2 (wherein R1 is an alkyl or alkenyl having 1 to 4 carbon atoms), NHCOR14 (wherein R14 is an alkyl having 1 to 4 carbon atoms which hydrogen may optionally be substituted with fluorine), hydroxy or OCOR15 (wherein R15 is an alkyl having 1 to 4 carbon atoms);
ZD is carboxy, COOR7xe2x80x2 (wherein R7xe2x80x2 is an alkyl having 1 to 4 carbon atoms) or CH2OR10xe2x80x2 (wherein R10xe2x80x2 is hydrogen or an acyl having 1 to 5 carbon atoms).
30) A ketone derivative of formula [1D] described in 1) above or a pharmacologically acceptable salt thereof, according to 29) described above, wherein:
AD is methyl;
BD is hydrogen;
XD is S;
YD is 2-acetylamino-2-carboxyethyl or 2-acetylamino-2-methoxycarbonylethyl; and,
ZD is carboxy, methoxycarbonyl, acetoxymethyl or hydroxymethyl.
31) A ketone derivative of formula [1D] described in 1) above or a pharmacologically acceptable salt thereof, according to 1) above, wherein:
AD is an unsubstituted or substituted aromatic hydrocarbon, aromatic heterocyclic ring or saturated heterocyclic ring;
BD is hydrogen or an unsubstituted or substituted aliphatic hydrocarbon group having 1 to 4 carbon atoms;
XD is S, O, or SO;
YD is an aliphatic hydrocarbon group having 1 to 6 carbon atoms (wherein at least one hydrogen is substituted with carboxy or a group derived therefrom, amino or a group derived therefrom or, hydroxy or a group derived therefrom); and,
ZD is carboxy or a group derived therefrom, an unsubstituted or substituted alkyl or alkenyl having 1 to 4 carbon atoms, hydroxy or a group derived therefrom, amino or a group derived therefrom, a monocyclic aromatic heterocyclic ring, a halogen or hydrogen.
32) A ketone derivative of formula [1D] described in 1) above or a pharmacologically acceptable salt thereof, according to 31) described above, wherein:
AD is an unsubstituted benzene ring wherein, when substituted, 1 to 3 hydrogen atoms are substituted with an unsubstituted or substituted alkyl group having 1 to 4 carbon atoms, a halogen, hydroxy, an alkoxy having 1 to 4 carbon atoms, amino, an alkyl- or dialkylamino having 1 to 4 carbon atoms, thiol, carboxy, an alkoxycarbonyl having 1 to 4 carbon atoms, an acyloxy having 1 to 5 carbon atoms, an acylthio having 1 to 5 carbon atoms, an acylamino having 1 to 5 carbon atoms, cyano or trifluoromethyl;
BD is hydrogen or an aliphatic hydrocarbon group having 1 to 4 carbon atoms;
XD is S, O, or SO;
YD is an aliphatic hydrocarbon group having 1 to 6 carbon atoms (wherein at least one hydrogen is substituted with carboxy, COOR1 (wherein R1 is a substituted or unsubstituted alkyl or alkenyl having 1 to 4 carbon atoms), CONR2R3 (wherein each of R2 and R3 which may be the same or different and independently represents hydrogen or an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), COW (wherein W is a heterocyclic ring which may be unsubstituted or substituted with carboxy or a group derived therefrom or, amino or a group derived therefrom), NR4R5 (wherein each of R4 and R5, which may be the same or different and independently represents hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or, an unsubstituted or substituted acyl having 1 to 5 carbon atoms) or OR6 (wherein R6 is hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or, an unsubstituted or substituted acyl having 1 to 5 carbon atoms); and,
ZD is carboxy, COOR7 (wherein R7 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), CONR8R9 (wherein each of R8 and R9, which may be the same or different and independently represents hydrogen or an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), cyano, CH2OR10 (wherein R10 is hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or, an unsubstituted or substituted acyl having 1 to 5 carbon atoms), hydroxy, OCOR11 (wherein R11 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), NR12R13 (wherein each of R12 and R13 which may be the same or different and independently represents hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or, an unsubstituted or substituted acyl having 1 to 5 carbon atoms), 5-tetrazolyl, chlorine, fluorine or hydrogen.
33) A ketone derivative of formula [1D] described in 1) above or a pharmacologically acceptable salt thereof, according to 32) described above, wherein:
AD is an unsubstituted or substituted benzene ring, wherein, when substituted, 1 to 3 hydrogen atoms are substituted with methyl, methoxy, methoxycarbonyl, nitro, cyano, a halogen or trifluoromethyl;
BD is hydrogen or an alkyl having 1 to 4 carbon atoms;
XD is S;
YD is an aliphatic hydrocarbon group having 1 to 6 carbon atoms (wherein at least two hydrogen atoms are substituted with carboxy, COOR1xe2x80x2 (wherein R1xe2x80x2 is an alkyl or alkenyl having 1 to 4 carbon atoms), NHCOR14 (wherein R14 is an alkyl having 1 to 4 carbon atoms which hydrogen may optionally be substituted with fluorine), hydroxy or OCOR15 (wherein R15 is an alkyl having 1 to 4 carbon atoms);
ZD is carboxy, COOR7xe2x80x2 (wherein R7xe2x80x2 is an alkyl having 1 to 4 carbon atoms) or CH2OR10xe2x80x2 (wherein R10xe2x80x2 is hydrogen or an acyl having 1 to 5 carbon atoms).
34) A ketone derivative of formula [1D] described in 1) above or a pharmacologically acceptable salt thereof, according to 33) described above, wherein:
AD is an unsubstituted benzene ring or a benzene ring substituted with methyl or methoxy;
BD is hydrogen;
XD is S;
YD is 2-acetylamino-2-carboxyethyl, 2-acetylamino-2-methoxycarbonylethyl or 2-acetylaminoethyl; and,
ZD is carboxy, methoxycarbonyl, acetoxymethyl or hydroxymethyl.
35) A ketone derivative of formula [1D] described in 1) above or a pharmacologically acceptable salt thereof, according to 1) above, wherein:
AD and BD are combined together to form an unsubstituted or substituted cycloalkan-1-one ring having 3 to 7 carbon atoms (except for 5 carbon atoms);
XD is S, O, or SO;
YD is an aliphatic hydrocarbon group having 1 to 6 carbon atoms (wherein at least one hydrogen is substituted with carboxy or a group derived therefrom, amino or a group derived therefrom or, hydroxy or a group derived therefrom); and,
ZD is carboxy or a group derived therefrom, an unsubstituted or substituted alkyl or alkenyl having 1 to 4 carbon atoms, hydroxy or a group derived therefrom, amino or a group derived therefrom, a monocyclic aromatic heterocyclic ring, a halogen or hydrogen.
36) A ketone derivative of formula [1D] described in 1) above or a pharmacologically acceptable salt thereof, according to 35) described above, wherein:
AD and BD are combined together to form an unsubstituted or substituted cyclobutan-1-one ring or cyclohexan-1-one ring;
XD is S, O, or SO;
YD is an aliphatic hydrocarbon group having 1 to 6 carbon atoms (wherein at least one hydrogen is substituted with carboxy, COOR1 (wherein R1 is a substituted or unsubstituted alkyl or alkenyl having 1 to 4 carbon atoms), CONR2R3 (wherein each of R2 and R3 which may be the same or different and independently represents hydrogen or an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), COW (wherein W is a heterocyclic ring which may be unsubstituted or substituted with carboxy or a group derived therefrom or, amino or a group derived therefrom), NR4R5 (wherein each of R4 and R5, which may be the same or different and independently represents hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or, an unsubstituted or substituted acyl having 1 to 5 carbon atoms) or OR6 (wherein R6 is hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or, an unsubstituted or substituted acyl having 1 to 5 carbon atoms); and,
ZD is carboxy, COOR7 (wherein R7 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), CONR8R9 (wherein each of R8 and R9, which may be the same or different and independently represents hydrogen or an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), cyano, CH2OR10 (wherein R10 is hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or, an unsubstituted or substituted acyl having 1 to 5 carbon atoms), hydroxy, OCOR11 (wherein R11 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), NR12R13 (wherein each of R12 and R13, which may be the same or different and independently represents hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or, an unsubstituted or substituted acyl having 1 to 5 carbon atoms), 5-tetrazolyl, chlorine, fluorine or hydrogen.
37) A ketone derivative of formula [1D] described in 1) above or a pharmacologically acceptable salt thereof, according to 36) described above, wherein:
AD and BD are combined together to form a cyclobutan-1-one ring or cyclohexan-1-one ring;
XD is S;
YD is an aliphatic hydrocarbon group having 1 to 6 carbon atoms (wherein at least two hydrogen atoms are substituted with carboxy, COOR1xe2x80x2 (wherein R1xe2x80x2 is an alkyl or alkenyl having 1 to 4 carbon atoms), NHCOR14 (wherein R14 is an alkyl having 1 to 4 carbon atoms which hydrogen may optionally be substituted with fluorine), hydroxy or OCOR15 (wherein R15 is an alkyl having 1 to 4 carbon atoms);
ZD is carboxy, COOR7xe2x80x2 (wherein R7xe2x80x2 is an alkyl having 1 to 4 carbon atoms) or CH2OR10xe2x80x2 (wherein R10xe2x80x2 is hydrogen or an acyl having 1 to 5 carbon atoms).
38) A ketone derivative of formula [1D] described in 1) above or a pharmacologically acceptable salt thereof, according to 37), wherein:
(I) AD and BD are combined together to form a cyclobutan-1-one ring, XD is S, YD is 2-acetylamino-2-carboxyethyl and, ZD is carboxy;
(II) AD and BD are combined together to form a cyclobutan-1-one ring, XD is S, YD is 2-acetylamino-2-methoxycarbonylethyl and, ZD is methoxycarbonyl;
(III) AD and BD are combined together to form a cyclobutan-1-one ring, XD is S, YD is 2,3-dihydroxy-n-propyl and, ZD is acetoxymethyl; and,
(IV) AD and BD are combined together to form a cyclohexan-1-one ring, XD is S, YD is 2-acetylamino-2-carboxyethyl and, ZD is carboxy.
39) A xcex2-di-substituted aminoketone derivative of formula [1F] described in 1) above or a pharmacologically acceptable salt thereof, according to 1) above, wherein:
AF is an unsubstituted or substituted aliphatic hydrocarbon group having 1 to 4 carbon atoms;
BF is hydrogen or, an unsubstituted or substituted aliphatic hydrocarbon group having 1 to 4 carbon atoms;
XF and YF are a straight or branched aliphatic hydrocarbon group having 1 to 10 carbon atoms (wherein at least one hydrogen may optionally be substituted with carboxy or a group derived therefrom, amino or a group derived therefrom or, hydroxy or a group derived therefrom) or; XF and YF are bound to each other directly or via a hetero atom to form a monocyclic heterocyclic ring (wherein at least one hydrogen may optionally be substituted with an alkyl having 1 to 4 carbon atoms, phenyl, carboxy or a group derived therefrom, amino or a group derived therefrom or, hydroxy or a group derived therefrom);
ZF is carboxy or a group derived therefrom, an unsubstituted or substituted alkyl or alkenyl having 1 to 4 carbon atoms, hydroxy or a group derived therefrom, amino or a group derived therefrom, a monocyclic aromatic heterocyclic ring or a halogen.
40) A xcex2-di-substituted aminoketone derivative of formula [1F] described in 1) above or a pharmacologically acceptable salt thereof, according to 39) described above, wherein:
AF is methyl, ethyl, n-propyl or isopropyl, which may be unsubstituted or substituted;
BF is hydrogen;
each of XF and YF, which may be the same or different and independently represents an alkyl having 1 to 6 carbon atoms or, XF and YF are bound to each other directly or via a hetero atom to form a monocyclic heteroaryl ring which may be unsubstituted or substituted with an alkyl having 1 to 4 carbon atoms or phenyl;
ZF is carboxy, COOR1 (wherein R1 is a substituted or unsubstituted alkyl having 1 to 4 carbon atoms or, phenyl), CONR2R3 (wherein each of R2 and R3, which may be the same or different and independently represents hydrogen or an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), cyano, CH2OR4 (wherein R4 is hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or, an unsubstituted or substituted acyl having 1 to 5 carbon atoms), hydroxy, OR5 (wherein R5 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or, an unsubstituted or substituted acyl having 1 to 5 carbon atoms), NR6R7 (wherein each of R6 and R7, which may be the same or different and independently represents hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or, an unsubstituted or substituted acyl having 1 to 5 carbon atoms), 5-tetrazolyl, chlorine or fluorine. 41) A xcex2-di-substituted aminoketone derivative of formula [1F] described in 1) above or a pharmacologically acceptable salt thereof, according to 40) described above, wherein:
AF is methyl;
BF is hydrogen;
XF and YF are both ethyl n-propyl or isopropyl, XF and YF are bound to each other directly or via a hetero atom to form a pyrrolidine, piperidine, morpholine, 4-methylpiperazine or 4-phenylpiperazine ring;
ZF is carboxy, COOR1xe2x80x2 (wherein R1xe2x80x2 is an alkyl having 1 to 4 carbon atoms), CONR2xe2x80x2R3xe2x80x2 (wherein R2xe2x80x2 and R3xe2x80x2, which may be the same or different and each is hydrogen or an alkyl having 1 to 4 carbon atoms) or cyano.
42) A xcex2-di-substituted aminoketone derivative of formula [1F] described in 1) above or a pharmacologically acceptable salt thereof, according to 1) above, wherein:
AF is an unsubstituted or substituted aryl, heteroaryl or saturated heterocyclic ring;
BF is hydrogen or, an unsubstituted or substituted aliphatic hydrocarbon group having 1 to 4 carbon atoms;
XF and YF are a straight or branched aliphatic hydrocarbon group having 1 to 10 carbon atoms (wherein at least one hydrogen may optionally be substituted with carboxy or a group derived therefrom, amino or a group derived therefrom or, hydroxy or a group derived therefrom) or, XF and YF are bound to each other directly or via a hetero atom to form a heterocyclic ring (wherein at least one hydrogen may optionally be substituted with an alkyl having 1 to 4 carbon atoms, phenyl, carboxy or a group derived therefrom, amino or a group derived therefrom or, hydroxy or a group derived therefrom);
ZF is carboxy or a group derived therefrom, an unsubstituted or substituted alkyl or alkenyl having 1 to 4 carbon atoms, hydroxy or a group derived therefrom, amino or a group derived therefrom, a monocyclic aromatic heterocyclic ring or a halogen.
43) A xcex2-di-substituted aminoketone derivative of formula [1F] described in 1) above or a pharmacologically acceptable salt thereof, according to 42) described above, wherein:
AF is an unsubstituted or substituted benzene ring or, monocyclic aromatic heterocyclic ring;
BF is hydrogen;
XF and YF, which may be the same or different, are a straight or branched aliphatic hydrocarbon group having 1 to 6 or, XF and YF are bound to each other directly or via a hetero atom to form a heterocyclic ring unsubstituted or substituted with an alkyl having 1 to 4 carbon atoms or phenyl;
ZF is carboxy, COOR1 (wherein R1 is a substituted or unsubstituted alkyl having 1 to 4 carbon atoms or, phenyl), CONR2R3 (wherein each of R2 and R3, which may be the same or different and independently represents hydrogen or an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), cyano, CH2OR4 (wherein R4 is hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or, an unsubstituted or substituted acyl having 1 to 5 carbon atoms), hydroxy, OR5 (wherein R5 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or, an unsubstituted or substituted acyl having 1 to 5 carbon atoms), NR6R7 (wherein each of R6 and R7, which may be the same or different and independently represents hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or, an unsubstituted or substituted acyl having 1 to 5 carbon atoms), 5-tetrazolyl, chlorine or fluorine.
44) A xcex2-di-substituted aminoketone derivative of formula [1F] described in 1) above or a pharmacologically acceptable salt thereof, according to 43) described above, wherein:
AF is an unsubstituted or substituted benzene ring wherein, when substituted, 1 to 3 hydrogen atoms are substituted with an alkyl having 1 to 4 carbon atoms, a halogen, hydroxy, an alkoxy having 1 to 4 carbon atoms, amino, an alkyl- or dialkylamino having 1 to 4 carbon atoms, thiol, carboxy, an alkoxycarbonyl having 1 to 4 carbon atoms, an acyloxy having 1 to 5 carbon atoms, an acylthio having 1 to 5 carbon atoms, an acylamino having 1 to 5 carbon atoms, cyano or trifluoromethyl;
BF is hydrogen;
each of XF and YF, which may be the same or different and independently represents an alkyl having 1 to 6 carbon atoms or, XF and YF are bound to each other directly or via a hetero atom to form a monocyclic heterocyclic ring unsubstituted or substituted with an alkyl having 1 to 4 carbon atoms or phenyl;
ZF is carboxy, COOR1xe2x80x2 (wherein R1xe2x80x2 is an alkyl having 1 to 4 carbon atoms), CONR2xe2x80x2R3xe2x80x2 (wherein R2xe2x80x2 and R3xe2x80x2 , which may be the same or different and each is hydrogen or an alkyl having 1 to 4 carbon atoms), cyano, or CH2OR4xe2x80x2 (wherein R4xe2x80x2 is hydrogen, an alkyl having 1 to 4 carbon atoms or an acyl having 1 to 5 carbon atoms).
45) A xcex2-di-substituted aminoketone derivative of formula [1F] described in 1) above or a pharmacologically acceptable salt thereof, according to 44) described above, wherein:
AF is an unsubstituted or substituted benzene ring, wherein, when substituted, 1 to 3 hydrogen atoms are substituted with methyl, methoxy, methoxycarbonyl, nitro, cyano, a halogen or trifluoromethyl;
BF is hydrogen;
XF and YF are both ethyl, n-propyl or isopropyl; or, XF and YF are bound to each other directly or via a hetero atom to form a pyrrolidine, piperidine, morpholine, 4-methylpiperazine or 4-phenylpiperazine ring;
ZF is carboxy, COOR1xe2x80x3 (wherein R1xe2x80x3 is methyl or ethyl), CONR2xe2x80x3R3xe2x80x3 (wherein R2xe2x80x3 and R3xe2x80x3, which may be the same or different and each is hydrogen, methyl or ethyl) or cyano.
46) A xcex2-di-substituted aminoketone derivative of formula [1F] described in 1) above or a pharmacologically acceptable salt thereof, according to 1) above, wherein:
AF and BF are combined together to form an unsubstituted or substituted cycloalkan-1-one ring having 3 to 7 carbon atoms or, AF and BF are combined together to form a cycloalkan-1-one ring having 3 to 7 carbon atoms, which ring is fused with an aromatic hydrocarbon or a aromatic heterocyclic ring.
XF and YF are a straight or branched aliphatic hydrocarbon group having 1 to 10 carbon atoms (wherein at least one hydrogen may optionally be substituted with carboxy or a group derived therefrom, amino or a group derived therefrom or, hydroxy or a group derived therefrom) or, XF and YF are bound to each other directly or via a hetero atom to form a heterocyclic ring (wherein at least one hydrogen may optionally be substituted with an alkyl having 1 to 4 carbon atoms, phenyl, carboxy or a group derived therefrom, amino or a group derived therefrom or, hydroxy or a group derived therefrom);
ZF is carboxy or a group derived therefrom, an unsubstituted or substituted alkyl or alkenyl having 1 to 4 carbon atoms, hydroxy or a group derived therefrom, amino or a group derived therefrom, a monocyclic aromatic heterocyclic ring or a halogen.
47) A xcex2-di-substituted aminoketone derivative of formula [1F] described in 1) above or a pharmacologically acceptable salt thereof, according to 46) described above, wherein:
AF and BF are combined together to form an unsubstituted or substituted cycloalkan-1-one ring having 4 to 6 carbon atoms or, to form an unsubstituted or substituted cycloalkan-1-one ring having 4 to 6 carbon atoms which is fused with an aromatic hydrocarbon or monocyclic aromatic heterocyclic ring;
each of XF and YF, which may be the same or different and independently is a straight or branched aliphatic hydrocarbon group having 1 to 6 carbon atoms or, XF and YF are bound to each other directly or via a hetero atom to form a monocyclic heterocyclic ring, which may be unsubstituted or substituted with an alkyl having 1 to 4 carbon atoms or phenyl;
ZF is carboxy, COOR1 (wherein R1 is a substituted or unsubstituted alkyl having 1 to 4 carbon atoms or, phenyl), CONR2R3 (wherein each of R2 and R3, which may be the same or different and independently represents hydrogen or an unsubstituted or substituted alkyl having 1 to 4 carbon atoms), cyano, CH2OR4 (wherein R4 is hydrogen, an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or, an unsubstituted or substituted acyl having 1 to 5 carbon atoms), hydroxy, OR5 (wherein R5 is an unsubstituted or substituted alkyl having 1 to 4 carbon atoms or, an unsubstituted or substituted acyl having 1 to 5 carbon atoms, preferably an alkyl having 1 to 4 carbon atoms or an acyl having 1 to 5 carbon atoms), NR6R7 (wherein each of R6 and R7, which may be the same or different and independently is hydrogen, an alkyl having 1 to 4 carbon atoms or an acyl having 1 to 5 carbon atoms), 5-tetrazolyl, chlorine or fluorine.
48) A xcex2-di-substituted aminoketone derivative of formula [1F] described in 1) above or a pharmacologically acceptable salt thereof, according to 47) described above, wherein:
AF and BF are combined together to form an unsubstituted or substituted cyclopentan-1-one ring or to form an unsubstituted or substituted cyclopentan-1-one ring fused with a benzene or monocyclic aromatic heterocyclic ring;
each of XF and YF, which may be the same or different and independently is an alkyl 1 to 6 carbon atoms or, XF and YF are bound to each other directly or via a hetero atom to form a monocyclic heteroaryl ring, which may be unsubstituted or substituted with an alkyl having 1 to 4 carbon atoms or phenyl;
ZF is carboxy, COOR1xe2x80x2 (wherein R1xe2x80x2 is an alkyl having 1 to 4 carbon atoms), CONR2xe2x80x2R3xe2x80x2 (wherein R2xe2x80x2 and R3xe2x80x2 , which may be the same or different and each is hydrogen or an alkyl having 1 to 4 carbon atoms), cyano or CH2OR4xe2x80x2 (wherein R4xe2x80x2 is hydrogen, an alkyl having 1 to 4 carbon atoms or an acyl having 1 to 5 carbon atoms).
49) A xcex2-di-substituted aminoketone derivative of formula [1F] described in 1) above or a pharmacologically acceptable salt thereof, according to 48) described above, wherein:
AF and BF are combined together to form a cyclopentan-1-one ring or indan-1-one ring;
XF and YF are both ethyl, n-propyl or isopropyl; or, XF and YF are bound to each other directly or via a hetero atom to form a pyrrolidine, piperidine, morpholine, 4-methylpiperazine or 4-phenylpiperazine ring; and,
ZF is carboxy, COOR1xe2x80x3 (wherein R1xe2x80x3 is methyl or ethyl), CONR2xe2x80x3R3xe2x80x3 (wherein R2xe2x80x3 and R3xe2x80x3 , which may be the same or different and each is hydrogen, methyl or ethyl) or cyano.
50) A pharmaceutical composition comprising as an effective ingredient a cyclopentanone derivative of formula [1A] according to 1) above or a cyclopentanone derivative according to any one of 2) through 6) described above, or a pharmacologically acceptable salt thereof, wherein the cyclopentanone derivative further includes:
(1) when Z1A and Z2A are hydrogen, XA is S, YA is methyl or benzyl and, Z3A is methoxycarbonyl,
(2) when Z1A and Z2A are hydrogen, XA is O or N, YA is benzyl and, Z3A is carboxy, methoxycarbonyl or ethoxycarbonyl;
(3) XA is N or O, Z1A and Z3A are hydrogen and, Z2A is carboxy or methoxycarbonyl;
(4) XA is O, Z1A is hydroxy or a group derived therefrom, Z2A is hydrogen and, Z3A is amino or a group derived therefrom;
(5) XA is S, Y1A is phenyl, Z1A is dimethoxymethyl and, Z2A and Z3A are hydrogen;
(6) XA is O, Y1A is methyl, Z1A is 1-methoxy-1-phenylthiomethyl and, Z2A and Z3A are hydrogen;
(7) Z1A is S, SO or SO2, Z2A is hydroxy or a group derived therefrom and, Z3A is hydrogen.
51) A composition for the treatment of central nervous disorders comprising as an effective ingredient a cyclopentanone derivative of formula [1A] according to 1) above or a cyclopentanone derivative according to any one of 2) through 6) described above, or a pharmacologically acceptable salt thereof, wherein the cyclopentanone derivative further includes:
(1) when Z1A and Z2A are hydrogen, XA is S, YA is methyl or benzyl and, Z3A is methoxycarbonyl,
(2) when Z1A and Z2A are hydrogen, XA is O or N, YA is benzyl and, Z3A is carboxy, methoxycarbonyl or ethoxycarbonyl;
(3) XA is N or O, Z1A and Z3A are hydrogen and, Z2A is carboxy or methoxycarbonyl;
(4) XA is O, Z1A is hydroxy or a group derived therefrom, Z2A is hydrogen and, Z3A is amino or a group derived therefrom;
(5) XA is S, Y1A is phenyl, Z1A is dimethoxymethyl and, Z2A and Z3A are hydrogen;
(6) XA is O, Y1A is methyl, Z1A is 1-methoxy-1-phenylthiomethyl and, Z2A and Z3A are hydrogen;
(7) Z1A is S, SO or SO2, Z2A is hydroxy or a group derived therefrom and, Z3A is hydrogen.
52) A composition for the treatment of peripheral nervous disorders comprising as an effective ingredient a cyclopentanone derivative of formula [1A] according to 1) above or a cyclopentanone derivative according to any one of 2) through 6) described above, or a pharmacologically acceptable salt thereof,wherein the cyclopentanone derivative further includes:
(1) when Z1A and Z2A are hydrogen, XA is S, YA is methyl or benzyl and, Z3A is methoxycarbonyl,
(2) when Z1A and Z2A are hydrogen, XA is O or N, YA is benzyl and, Z3A is carboxy, methoxycarbonyl or ethoxycarbonyl;
(3) XA is N or O, Z1A and Z3A are hydrogen and, Z2A is carboxy or methoxycarbonyl;
(4) XA is O, Z1A is hydroxy or a group derived therefrom, Z2A is hydrogen and, Z3A is amino or a group derived therefrom;
(5) XA is S, Y1A is phenyl, Z1A is dimethoxymethyl and, Z2A and Z3A are hydrogen;
(6) XA is O, Y1A is methyl, Z1A is 1-methoxy-1-phenylthiomethyl and, Z2A and Z3A are hydrogen;
(7) Z1A is S, SO or SO2, Z2A is hydroxy or a group derived therefrom and, Z3A is hydrogen.
53) A composition for promoting nerve cell differentiation comprising as an effective ingredient a cyclopentanone derivative of formula [1A] according to 1) above or a cyclopentanone derivative according to any one of 2) through 6) described above, or a pharmacologically acceptable salt thereof, wherein the cyclopentanone derivative further includes:
(1) when Z1A and Z2A are hydrogen, XA is S, YA is methyl or benzyl and, Z3A is methoxycarbonyl,
(2) when Z1A and Z2A are hydrogen, XA is O or N, YA is benzyl and, Z3A is carboxy, methoxycarbonyl or ethoxycarbonyl;
(3) XA is N or O, Z1A and Z3A are hydrogen and, Z2A is carboxy or methoxycarbonyl;
(4) XA is O, Z1A is hydroxy or a group derived therefrom, Z2A is hydrogen and, Z3A is amino or a group derived therefrom;
(5) XA is S, Y1A is phenyl, Z1A is dimethoxymethyl and, Z2A and Z3A are hydrogen;
(6) XA is O, Y1A is methyl, Z1A is 1-methoxy-1-phenylthiomethyl and, Z2A and Z3A are hydrogen;
(7) Z1A is S, SO or SO2, Z2A is hydroxy or a group derived therefrom and, Z3A is hydrogen.
54) A pharmaceutical composition comprising as an effective ingredient a 2,3-di-substituted cyclopentanone derivative of formula [1B] described in 1) above or a 2,3-di-substituted cyclopentanone derivative according to any one of 7) through 18) described above, or a pharmacologically acceptable salt thereof.
55) A composition for the treatment of central nervous disorders comprising as an effective ingredient a 2,3-di-substituted cyclopentanone derivative of formula [1B] described in 1) above or a 2,3-di-substituted cyclopentanone derivative according to any one of 7) through 18) described above, or a pharmacologically acceptable salt thereof.
56) A composition for the treatment of peripheral nervous disorders comprising as an effective ingredient a 2,3-di-substituted cyclopentanone derivative of formula [1B] described in 1) above or a 2,3-di-substituted cyclopentanone derivative according to any one of 7) through 18), or a pharmacologically acceptable salt thereof.
57) A composition for promoting nerve cell differentiation comprising as an effective ingredient a 2,3-di-substituted cyclopentanone derivative of formula [1B] described in 1) above or a 2,3-di-substituted cyclopentanone derivative according to any one of 7) through 18), or a pharmacologically acceptable salt thereof.
58) A pharmaceutical composition comprising as an effective ingredient a cyclopentenone derivative of formula [1C] described in 1) above or a cyclopentenone derivative according to any one of 19) through 26), or a pharmacologically acceptable salt thereof, wherein said cyclopentenone derivative further includes the cases that when Xc is O or NH, Z1c and Z3c are hydrogen and, Z2c is hydrogen or, hydroxy or a group derived therefrom.
59) A composition for the treatment of central nervous disorders comprising as an effective ingredient a cyclopentenone derivative of formula [1C] described in 1) above or a cyclopentenone derivative according to any one of 19) through 26) described above, or a pharmacologically acceptable salt thereof, wherein said cyclopentenone derivative further includes the cases that when Xc is O or NH, Z1c and Z3c are hydrogen and, Z2c is hydrogen or, hydroxy or a group derived therefrom.
60) A composition for the treatment of peripheral nervous disorders comprising as an effective ingredient a cyclopentenone derivative of formula [1C] described in 1) above or a cyclopentenone derivative according to any one of 19) through 26) described above, or a pharmacologically acceptable salt thereof, wherein said cyclopentenone derivative further includes the cases that when Xc is O or NH, Z1c and Z3c are hydrogen and, Z2c is hydrogen or, hydroxy or a group derived therefrom.
61) A composition for promoting nerve cell differentiation comprising as an effective ingredient a cyclopentenone derivative of formula [1C] described in 1) above or a cyclopentenone derivative according to any one of 19) through 26) described above, or a pharmacologically acceptable salt thereof, wherein said cyclopentenone derivative further includes the cases that when Xc is O or NH, Z1c and Z3c are hydrogen and, Z2c is hydrogen or, hydroxy or a group derived therefrom.
62) A pharmaceutical composition comprising as an effective ingredient a ketone derivative of formula [1D] according to 1) above or a ketone derivative according to any one of 26) through 38) described above, or a pharmacologically acceptable salt thereof, wherein, when AD and BD are combined together to form a cyclobutane ring, the ketone derivative further includes (1) through (4):
(1) XD is O, YD is methyl, n-octyl or n-hexadecyl and, ZD is methoxycarbonyl;
(2) XD is O, YD is benzyl and, ZD is benzyloxylmethyl;
(3) XD is O, YD is p-methoxybenzyl and, ZD is p-methoxybenzyloxymethyl; and,
(4) XD is O, YD is trityl and ZD is trityloxymethyl and when AD is an unsubstituted benzene ring and BD is hydrogen, XD is S, YD is methyl, ethyl or isopropyl and ZD is carboxy.
63) A composition for the treatment of central nervous disorders comprising as an effective ingredient a ketone derivative of formula [1D] according to 1) above or a ketone derivative according to any one of 26) through 38) described above, or a pharmacologically acceptable salt thereof, wherein, when AD and BD are combined together to form a cyclobutane ring, the ketone derivative further includes (1) through (4):
(1) XD is O, YD is methyl, n-octyl or n-hexadecyl and, ZD is methoxycarbonyl;
(2) XD is O, YD is benzyl and, ZD is benzyloxylmethyl;
(3) XD is O, YD is p-methoxybenzyl and, ZD is p-methoxybenzyloxymethyl; and,
(4) XD is O, YD is trityl and ZD is trityloxymethyl and when AD is an unsubstituted benzene ring and BD is hydrogen, XD is S, YD is methyl, ethyl or isopropyl and ZD is carboxy.
64) A composition for the treatment of peripheral nervous disorders comprising as an effective ingredient a ketone derivative of formula [1D] according to 1) above or a ketone derivative according to any one of 26) through 38) described above, or a pharmacologically acceptable salt thereof, wherein, when AD and BD are combined together to form a cyclobutane ring, the ketone derivative further includes (1) through (4):
(1) XD is O, YD is methyl, n-octyl or n-hexadecyl and, ZD is methoxycarbonyl;
(2) XD is O, YD is benzyl and, ZD is benzyloxylmethyl;
(3) XD is O, YD is p-methoxybenzyl and, ZD is p-methoxybenzyloxymethyl; and,
(4) XD is O, YD is trityl and ZD is trityloxymethyl and when AD is an unsubstituted benzene ring and BD is hydrogen, XD is S, YD is methyl, ethyl or isopropyl and ZD is carboxy.
65) A composition for promoting nerve cell differentiation comprising as an effective ingredient a ketone derivative of formula [1D] according to 1) above or a ketone derivative according to any one of 26) through 38) described above, or a pharmacologically acceptable salt thereof, wherein, when AD and BD are combined together to form a cyclobutane ring, the ketone derivative further includes (1) through (4):
(1) XD is O, YD is methyl, n-octyl or n-hexadecyl and, ZD is methoxycarbonyl;
(2) XD is O, YD is benzyl and, ZD is benzyloxylmethyl;
(3) XD is O, YD is p-methoxybenzyl and, ZD is p-methoxybenzyloxymethyl; and,
(4) XD is O, YD is trityl and ZD is trityloxymethyl and when AD is an unsubstituted benzene ring and BD is hydrogen, XD is S, YD is methyl, ethyl or isopropyl and ZD is carboxy.
66) A pharmaceutical composition comprising as an effective ingredient a compound of formula [1E] according to 1) above or a pharmacologically acceptable salt thereof.
67) A composition for the treatment of central nervous disorders comprising as an effective ingredient a compound of formula [1E] according to 1) above or a pharmacologically acceptable salt thereof.
68) A composition for the treatment of peripheral nervous disorders comprising as an effective ingredient a compound of formula [1E] according to 1) above or a pharmacologically acceptable salt thereof.
69) A composition for promoting nerve cell differentiation comprising as an effective ingredient a compound of formula [1E] according to 1) above or a pharmacologically acceptable salt thereof.
70) A pharmaceutical composition comprising as an effective ingredient a xcex2-di-substituted aminoketone derivative of formula [1F] according to 1) above or xcex2-di-substituted aminoketone derivative according to any of 39)xcx9c49) described above, or a pharmacologically acceptable salt thereof, wherein, when AF is an unsubstituted benzene ring, the xcex2-di-substituted aminoketone derivative further includes those wherein BFis hydrogen, XF is bound directly to YF to form a piperidine ring and, ZF is carboxy.
71) A composition for the treatment of central nervous disorders comprising as an effective ingredient a xcex2-di-substituted aminoketone derivative of formula [1F] according to 1) above or a xcex2-di-substituted aminoketone derivative according to any of 39)xcx9c49) described above, or a pharmacologically acceptable salt thereof, wherein, when AF is an unsubstituted benzene ring, the xcex2-di-substituted aminoketone derivative further includes those wherein BF is hydrogen, XF is directly bound to YF to form a piperidine ring and, ZF is carboxy.
72) A composition for the treatment of peripheral nervous disorders comprising as an effective ingredient a xcex2-di-substituted aminoketone derivative of formula [1F] according to 1) above or a xcex2-di-substituted aminoketone derivative according to any of 39)xcx9c49) described above, or a pharmacologically acceptable salt thereof, wherein, when AF is an unsubstituted benzene ring, the xcex2-di-substituted aminoketone derivative further includes those wherein BF is hydrogen, XF is directly bound to YF to form a piperidine ring and, ZF is carboxy.
73) A composition for promoting nerve cell differentiation comprising as an effective ingredient a xcex2-di-substituted aminoketone derivative of formula [1F] according to 1) above or a xcex2-di-substituted aminoketone derivative according to any of 39)xcx9c49) described above, or a pharmacologically acceptable salt thereof, wherein, when AF is an unsubstituted benzene ring, the xcex2-di-substituted aminoketone derivative further includes those wherein BF is hydrogen, XF is directly bound to YF to form a piperidine ring and, ZF is carboxy.